RESUMO
Pericytes are skeletal muscle resident, multipotent stem cells that are localized to the microvasculature. In vivo, studies have shown that they respond to damage through activation of nuclear-factor kappa-B (NF-κB), but the downstream effects of NF-κB activation on endothelial cell proliferation and cell-cell signaling during repair remain unknown. The purpose of this study was to examine pericyte NF-κB activation in a model of skeletal muscle damage; and use genetic manipulation to study the effects of changes in pericyte NF-κB activation on endothelial cell proliferation and cytokine secretion. We utilized scratch injury to C2C12 cells in coculture with human primary pericytes to assess NF-κB activation and monocyte chemoattractant protein-1 (MCP-1) secretion from pericytes and C2C12 cells. We also cocultured endothelial cells with pericytes that expressed genetically altered NF-κB activation levels, and then quantified endothelial cell proliferation and screened the conditioned media for secreted cytokines. Pericytes trended toward greater NF-κB activation in injured compared to control cocultures (P = 0.085) and in comparison to C2C12 cells (P = 0.079). Second, increased NF-κB activation in pericytes enhanced the proliferation of cocultured endothelial cells (1.3-fold, P = 0.002). Finally, we identified inflammatory signaling molecules, including MCP-1 and interleukin 8 (IL-8) that may mediate the crosstalk between pericytes and endothelial cells. The results of this study show that pericyte NF-κB activation may be an important mechanism in skeletal muscle repair with implications for the development of therapies for musculoskeletal and vascular diseases, including peripheral artery disease.
RESUMO
PURPOSE: This study compared endurance and neuromuscular function after bouts of low-load (LL), high-load (HL), and LL blood flow-restricted (LL(BFR)) resistance exercise. METHODS: Eight recreationally active male subjects completed three sets of dynamic knee extensions to volitional failure under three conditions: HL (70% peak torque), LL (20% peak torque), and LL(BFR) (20% peak torque with an occlusive cuff inflated to 180 mm Hg wrapped around the thigh). Before and immediately after exercise, isometric torque, central activation, electrically evoked torque, and muscle activation via surface EMG were measured. RESULTS: Isometric torque and evoked torque decreased an average of 37% and 40%, respectively (P < 0.01) in all conditions after exercise. There were no differences in the toque decrements between the conditions (P > 0.05). Percent central activation did not change after any condition (P = 0.09). Rate of torque development declined an average of 26% after all three conditions (P = 0.003), and rate of half-relaxation time was depressed by 48% after the HL condition (P = 0.004) only. EMG amplitude was greater in the HL condition at the beginning and end of exercise compared with the LL and LL(BFR) conditions (P = 0.001). At the end of exercise, EMG amplitude rose 19% (P = 0.02) and was not different among conditions (P > 0.05). Subjects performed more repetitions during the LL and LL(BFR) conditions (P < 0.05). CONCLUSION: Although LL and LL(BFR) resistance exercise to volitional failure exhibit lower levels of muscle activation than HL exercise, similar torque decrements occur after all bouts of resistance exercise, and the muscle fatigue can be attributed to peripheral factors.
